Conformational modulation of sequence recognition in synthetic macromolecules

The different triplet sequences in high molecular weight aromatic copolyimides comprising pyromellitimide units ("I") flanked by either ether-ketone ("K") or ether-sulfone residues ("S") show different binding strengths for pyrene-based tweezer-molecules. Such molecules bind primarily to the diimide unit through complementary π-π-stacking and hydrogen bonding. However, as shown by the magnitudes of 1H NMR complexation shifts and tweezer-polymer binding constants, the triplet "SIS" binds tweezer-molecules more strongly than "KIS" which in turn bind such molecules more strongly than "KIK". Computational models for tweezer-polymer binding, together with single-crystal X-ray analyses of tweezer-complexes with macrocyclic ether-imides, reveal that the variations in binding strength between the different triplet sequences arise from the different conformational preferences of aromatic rings at diarylketone and diarylsulfone linkages. These preferences determine whether or not chain-folding and secondary π−π-stacking occurs between the arms of the tweezermolecule and the 4,4'-biphenylene units which flank the central diimide residue.

Using cursor measures to determine appropriate computer input assistance for motion-impaired users

People with motion-impairments can often have difficulty with accurate control of standard pointing devices for computer input. The nature of the difficulties may vary, so to be most effective, methods of assisting cursor control must be suited to each user's needs. The work presented here involves a study of cursor trajectories as a means of assessing the requirements of motion-impaired computer users. A new cursor characteristic is proposed that attempts to capture difficulties with moving the cursor in a smooth trajectory. A study was conducted to see if haptic tunnels could improve performance in "point and click" tasks. Results indicate that the tunnels reduced times to target for those users identified by the new characteristic as having the most difficulty moving in a smooth trajectory. This suggests that cursor characteristics have potential applications in performing assessments of a user's cursor control capabilities which can then be used to determine appropriate methods of assistance.

Improving sequence-based fold recognition by using 3D model quality assessment

Motivation: The ability of a simple method (MODCHECK) to determine the sequence–structure compatibility of a set of structural models generated by fold recognition is tested in a thorough benchmark analysis. Four Model Quality Assessment Programs (MQAPs) were tested on 188 targets from the latest LiveBench-9 automated structure evaluation experiment. We systematically test and evaluate whether the MQAP methods can successfully detect native-likemodels. Results: We show that compared with the other three methods tested MODCHECK is the most reliable method for consistently performing the best top model selection and for ranking the models. In addition, we show that the choice of model similarity score used to assess a model's similarity to the experimental structure can influence the overall performance of these tools. Although these MQAP methods fail to improve the model selection performance for methods that already incorporate protein three dimension (3D) structural information, an improvement is observed for methods that are purely sequence-based, including the best profile–profile methods. This suggests that even the best sequence-based fold recognition methods can still be improved by taking into account the 3D structural information.

Prediction of novel and analogous folds using fragment assembly and fold recognition

A number of new and newly improved methods for predicting protein structure developed by the Jones–University College London group were used to make predictions for the CASP6 experiment. Structures were predicted with a combination of fold recognition methods (mGenTHREADER, nFOLD, and THREADER) and a substantially enhanced version of FRAGFOLD, our fragment assembly method. Attempts at automatic domain parsing were made using DomPred and DomSSEA, which are based on a secondary structure parsing algorithm and additionally for DomPred, a simple local sequence alignment scoring function. Disorder prediction was carried out using a new SVM-based version of DISOPRED. Attempts were also made at domain docking and “microdomain” folding in order to build complete chain models for some targets.

Benchmarking secondary structure prediction for fold recognition

If secondary structure predictions are to be incorporated into fold recognition methods, an assessment of the effect of specific types of errors in predicted secondary structures on the sensitivity of fold recognition should be carried out. Here, we present a systematic comparison of different secondary structure prediction methods by measuring frequencies of specific types of error. We carry out an evaluation of the effect of specific types of error on secondary structure element alignment (SSEA), a baseline fold recognition method. The results of this evaluation indicate that missing out whole helix or strand elements, or predicting the wrong type of element, is more detrimental than predicting the wrong lengths of elements or overpredicting helix or strand. We also suggest that SSEA scoring is an effective method for assessing accuracy of secondary structure prediction and perhaps may also provide a more appropriate assessment of the “usefulness” and quality of predicted secondary structure, if secondary structure alignments are to be used in fold recognition.

What are the baselines for protein fold recognition?

What constitutes a baseline level of success for protein fold recognition methods? As fold recognition benchmarks are often presented without any thought to the results that might be expected from a purely random set of predictions, an analysis of fold recognition baselines is long overdue. Given varying amounts of basic information about a protein—ranging from the length of the sequence to a knowledge of its secondary structure—to what extent can the fold be determined by intelligent guesswork? Can simple methods that make use of secondary structure information assign folds more accurately than purely random methods and could these methods be used to construct viable hierarchical classifications?

A multinomial model of applying recognition to judge between multiple alternatives

Proponents of the “fast and frugal” approach to decision-making suggest that inferential judgments are best made on the basis of limited information. For example, if only one of two cities is recognized and the task is to judge which city has the larger population, the recognition heuristic states that the recognized city should be selected. In preference choices with >2 options, it is also standard to assume that a “consideration set”, based upon some simple criterion, is established to reduce the options available. A multinomial processing tree model is outlined which provides the basis for estimating the extent to which recognition is used as a criterion in establishing a consideration set for inferential judgments.

Empathy and emotion recognition in people with autism, first-degree relatives, and controls

Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p<0.05) but not mothers (p>0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p<0.001) than controls. On the KDEF, statistical analyses revealed poorer overall performance by adults with ASC (p<0.001) compared to the control group. When the 6 distinct basic emotions were analysed separately, the ASC group showed impaired performance across five out of six expressions (happy, sad, angry, afraid and disgusted). Parents of a child with ASC were not significantly worse than controls at recognising any of the basic emotions, after controlling for age and non-verbal IQ (all p>0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p<0.05) but not for self-reported empathy (p>0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed.

The neurochemically diverse intermedius nucleus of the medulla as a source of excitatory and inhibitory synaptic input to the nucleus tractus solitarii

Sensory afferent signals from neck muscles have been postulated to influence central cardiorespiratory control as components of postural reflexes, but neuronal pathways for this action have not been identified. The intermedius nucleus of the medulla (InM) is a target of neck muscle spindle afferents and is ideally located to influence such reflexes but is poorly investigated. To aid identification of the nucleus, we initially produced three-dimensional reconstructions of the InM in both mouse and rat. Neurochemical analysis including transgenic reporter mice expressing green fluorescent protein in GABA-synthesizing neurons, immunohistochemistry, and in situ hybridization revealed that the InM is neurochemically diverse, containing GABAegric and glutamatergic neurons with some degree of colocalization with parvalbumin, neuronal nitric oxide synthase, and calretinin. Projections from the InM to the nucleus tractus solitarius (NTS) were studied electrophysiologically in rat brainstem slices. Electrical stimulation of the NTS resulted in antidromically activated action potentials within InM neurons. In addition, electrical stimulation of the InM resulted in EPSPs that were mediated by excitatory amino acids and IPSPs mediated solely by GABA(A) receptors or by GABA(A) and glycine receptors. Chemical stimulation of the InM resulted in (1) a depolarization of NTS neurons that were blocked by NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonoamide) or kynurenic acid and (2) a hyperpolarization of NTS neurons that were blocked by bicuculline. Thus, the InM contains neurochemically diverse neurons and sends both excitatory and inhibitory projections to the NTS. These data provide a novel pathway that may underlie possible reflex changes in autonomic variables after neck muscle spindle afferent activation.

Inferring the biggest and best: a measurement model for applying recognition to evoke consideration sets and judge between multiple alternatives

It has long been supposed that preference judgments between sets of to-be-considered possibilities are made by means of initially winnowing down the most promising-looking alternatives to form smaller “consideration sets” (Howard, 1963; Wright & Barbour, 1977). In preference choices with >2 options, it is standard to assume that a “consideration set”, based upon some simple criterion, is established to reduce the options available. Inferential judgments, in contrast, have more frequently been investigated in situations in which only two possibilities need to be considered (e.g., which of these two cities is the larger?) Proponents of the “fast and frugal” approach to decision-making suggest that such judgments are also made on the basis of limited, simple criteria. For example, if only one of two cities is recognized and the task is to judge which city has the larger population, the recognition heuristic states that the recognized city should be selected. A multinomial processing tree model is outlined which provides the basis for estimating the extent to which recognition is used as a criterion in establishing a consideration set for inferential judgments between three possible options.

Recognition of "difference" in Shari'a: a feminist scrutiny through the lens of substantive equality

The paper looks at the works of notable Islamic feminists to examine whether Islam can be reconciled with a substantive approach to gender equality. Located within contemporary feminist debates related to gender equality, it considers the Qur’anic verses related to two controversial areas of Shari’a law, namely, duty of obedience and polygamy, to explore how Islamic scriptures perceive ‘difference’ and its implications for substantive equality-based legal reforms in a Muslim society.

Input quality matters: some comments on input type and age-effects in adult SLA.

In accord with the general program of researching factors relating to ultimate attainment and maturational constraints in adult language acquisition, this commentary highlights the importance of input differences in amount, type, and setting between naturalistic and classroom learners of an L2. It is suggested that these variables are often confounded with age factors. Herein, we wish to call attention to the possible deterministic role that the differences in the grammatical quality of classroom input have on development and on competence outcomes. Framing what we see as greater formal complexity of the learning task for classroom learners, we suggest that one might benefit from focusing less on difference and more on how classroom L2 learners, at least some of them, come to acquire all that they do despite crucial qualitative differences in their input.

Heritage speaker competence differences, language change and input type: inflected infinitives in Heritage Brazilian Portuguese

It has been argued that colloquial dialects of Brazilian Portuguese (BP) have undergone significant linguistic change resulting in the loss of inflected infinitives (e.g., Pires, 2002, 2006). Since BP adults, at least educated ones, have complete knowledge of inflected infinitives, the implicit claim is that they are transmitted via formal education in the standard dialect. In the present article, I test one of the latent predictions of such claims; namely, the fact that heritage speakers of BP who lack formal education in the standard dialect should never develop native-like knowledge of inflected infinitives. In doing so, I highlight two significant implications (a) that heritage speaker grammars are a good source for testing dialectal variation and language change proposals and (b) incomplete acquisition and/or attrition are not the only sources of heritage language competence differences. Employing the syntactic and semantic tests of Rothman and Iverson (2007), I compare heritage speakers' knowledge to Rothman and Iverson's advanced adult L2 learners and educated native controls. Unlike the latter groups, the data for heritage speakers indicate that they do not have target knowledge of inflected infinitives, lending support to Pires' claims, suggesting that literacy plays a significant role in the acquisition of this grammatical property in BP.

Input type and parameter resetting: is naturalistic input necessary?

It has been argued that extended exposure to naturalistic input provides L2 learners with more of an opportunity to converge of target morphosyntactic competence as compared to classroom-only environments, given that the former provide more positive evidence of less salient linguistic properties than the latter (e.g., Isabelli 2004). Implicitly, the claim is that such exposure is needed to fully reset parameters. However, such a position conflicts with the notion of parameterization (cf. Rothman and Iverson 2007). In light of two types of competing generative theories of adult L2 acquisition – the No Impairment Hypothesis (e.g., Duffield and White 1999) and so-called Failed Features approaches (e.g., Beck 1998; Franceschina 2001; Hawkins and Chan 1997), we investigate the verifiability of such a claim. Thirty intermediate L2 Spanish learners were tested in regards to properties of the Null-Subject Parameter before and after study-abroad. The data suggest that (i) parameter resetting is possible and (ii) exposure to naturalistic input is not privileged.